22. Biochemistry | Metabolism - Pathways

How many kcal/gram are released from fats?

9 kcal/gram

How many kcal/gram are released from carbohydrates and proteins?

4 kcal/gram

How is the oxidative state of a molecule determined?

By an increase in oxygen or a decrease in hydrogen attached to carbon

Which molecule is the metabolic convergence point for carbohydrates, fats, and amino acids?

Acetyl-CoA

What are the two fates of Acetyl-CoA in metabolism?

1. Enters TCA cycle and OXPHOS to generate ATP; 2. Converted into ketone bodies during starvation

What is the substrate and product of Glycolysis?

Glucose→ Pyruvate

Where does Glycolysis occur?

Cytosol

What is the substrate and product of Anaerobic Glycolysis?

Pyruvate→ Lactate

Where does Anaerobic Glycolysis occur?

Cytosol

What is the substrate and product of Aerobic Glycolysis?

Pyruvate + O2→ Acetyl-CoA→ CO2 + NADH

Where does Aerobic Glycolysis occur?

Mitochondria

What is the substrate and product of the Pentose Phosphate Pathway (PPP)?

Glucose-6P→ NADPH + Ribose-5P

Where does the Pentose Phosphate Pathway (PPP) occur?

Cytosol

What is the substrate and product of Gluconeogenesis?

Pyruvate, amino acids, lactate→ Glucose

Where does Gluconeogenesis occur?

Cytosol and mitochondria

What is the substrate and product of β-Oxidation?

Fatty acids→ Acetyl-CoA

Where does β-Oxidation occur?

Mitochondria

What is the substrate and product of Ketogenesis?

Acetyl-CoA→ Ketone Bodies

Where does Ketogenesis occur?

Mitochondria (liver)

What is the substrate and product of the Urea Cycle?

NH3 from amino acids→ Urea

Where does the Urea Cycle occur?

Cytosol and mitochondria

What is the brain's primary energy source 4-10 hours after eating?

Glucose from liver glycogen stores

What is the brain's primary energy source 1-7 days after eating?

Glucose from gluconeogenesis using amino acids

What is the brain's primary energy source after 1 week of starvation?

Ketone bodies (β-hydroxybutyrate, acetoacetate)

How does the brain's reliance on glucose change after 1 week of starvation?

It decreases due to increased use of ketone bodies

What is the hormone profile in the fed state?

High insulin, low glucagon

What is the primary metabolism in the fed state?

Storage: glycogenesis, lipogenesis, protein synthesis, glycolysis

What is the brain's fuel source in the fed state?

Glucose

What is the hormone profile in the fasted state?

Low insulin, high glucagon

What is the primary metabolism in the fasted state?

Mobilization: glycogenolysis, gluconeogenesis, lipolysis

What is the brain's fuel source in the fasted state?

Glucose from liver

What is the hormone profile in the starvation state?

Very low insulin, very high glucagon

What is the primary metabolism in the starvation state?

Gluconeogenesis from amino acids, ketogenesis from fatty acids

What is the brain's fuel source in the starvation state?

Ketone bodies

What processes are active in the liver during the fed state?

Glycogenesis, lipogenesis, protein synthesis

What processes are active in the liver during the fasted/starved state?

Glycogenolysis, gluconeogenesis, ketogenesis

What processes are active in muscle during the fed state?

Glycogen storage, protein synthesis

What processes are active in muscle during the fasted/starved state?

Glycogenolysis for self, BCAA use, ketone use during starvation

What processes are active in adipose tissue during the fed state?

Lipogenesis (fat storage)

What processes are active in adipose tissue during the fasted/starved state?

Lipolysis (release of free fatty acids into blood)

What processes are active in the brain during the fed state?

Glucose uptake from blood (no storage)

What processes are active in the brain during the fasted/starved state?

Glucose use from liver initially, ketone use after 1 week

What is the source of insulin?

Pancreatic β-cells

What is the source of glucagon?

Pancreatic α-cells

What is the source of epinephrine?

Adrenal medulla

What is the source of cortisol?

Adrenal cortex

What is the source of thyroid hormones?

Thyroid gland

When is insulin most active?

Fed state

When is glucagon most active?

Fasted/starved state

When is epinephrine most active?

Stress state

When is cortisol most active?

Long-term stress

When are thyroid hormones most active?

Chronic regulation

What are the major actions of insulin?

Promotes glucose uptake, glycogenesis, lipogenesis, protein synthesis, glycolysis

What are the major actions of glucagon?

Stimulates glycogenolysis, gluconeogenesis, lipolysis

What are the major actions of epinephrine?

Triggers glycogenolysis and gluconeogenesis (fight/flight response)

What are the major actions of cortisol?

Supports gluconeogenesis, inhibits protein synthesis via nuclear receptors

What are the major actions of thyroid hormones?

Increase basal metabolic rate, stimulate thermogenesis via UCP1

Which metabolic pathways occur in the cytosol?

Glycolysis, PPP, fatty acid synthesis

Which metabolic pathways occur in the mitochondria?

β-oxidation, TCA cycle, OXPHOS, ketogenesis

Which metabolic pathways occur in both cytosol and mitochondria?

Gluconeogenesis, urea cycle

What causes lactic acidosis and what are its features?

Excess lactate lowers pH (<7.35); presents with shallow breathing and increased anion gap

How is the anion gap calculated?

[Na+] - ([Cl-] + [HCO3-])

What causes ketoacidosis and what are its features?

Excess ketone bodies (from diabetes, starvation, alcoholism); presents with acidic blood and fruity breath

What causes alcoholic ketoacidosis?

Alcohol impairs gluconeogenesis, increasing reliance on ketogenesis

A 45-year-old woman is given a drug that blocks carnitine transport into mitochondria. Which of the following metabolic effects is expected in her hepatocytes after 24 hours of fasting?

A. Increased ketogenesis
B. Decreased β-oxidation
C. Increased gluconeogenesis from fatty acids
D. Increased production of ribose-5-phosphate
E. Increased conversion of acetyl-CoA into glucose

B

• A. Increased ketogenesis ❌ – Ketogenesis requires β-oxidation to generate acetyl-CoA; without carnitine, FA cannot enter mitochondria, so ketogenesis ↓.

• B. Decreased β-oxidation ✅ – Carnitine shuttle defect = no fatty acid oxidation = ↓ acetyl-CoA, ↓ ketones.

• C. Gluconeogenesis from fatty acids ❌ – Fatty acids cannot be converted into glucose (only odd-chain FA can yield propionyl-CoA → succinyl-CoA).

• D. Ribose-5-phosphate ❌ – Product of PPP, unrelated.

• E. Acetyl-CoA → glucose ❌ – Impossible; acetyl-CoA cannot be converted back into glucose